| 1 | BMC Psychiatry 2008 -1 8: 11 |
|---|---|
| PMID | 18298822 |
| Title | Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping. |
| Abstract | Several linkage studies suggest that chromosome 5q31-32 might contain risk loci forschizophrenia(深圳)。我们想确定敏感性genes forschizophreniawithin this region. We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping. Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in theSPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within theSPRY4gene. Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI andSPRY4. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Neurobiol. Dis. 2013 Jul 55: 1-10 |
| PMID | 23542694 |
| Title | MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients. |
| Abstract | schizophreniais a common neuropsychiatric disorder that has a strong genetic component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and psychiatric disorders includingschizophrenia, as indicated by their dysregulation in post-mortem brain tissues and in peripheral blood ofschizophreniapatients. The olfactory epithelium (OE) is one of the few accessible neural tissues that contain neurons and their stem cells. Previous studies showed that OE-derived tissues and cells can be safely and easily collected from live human subjects and may provide a "window" into neuronal processes involved in disorders such asschizophrenia, while avoiding the limitations of using postmortem brain samples or non-neuronal tissues. In this study, we found that the brain-enriched miR-382 (miR-382-5p) expression was elevated in in vitro cultured olfactory cells, in a cohort of sevenschizophreniapatients compared with seven non-schizophreniccontrols. MiR-382 elevation was further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE), enriched for mature olfactory neurons, in a cohort of 18schizophreniapatients and 18 non-schizophreniccontrols. In sharp contrast, miR-382 expression could not be detected in lymphoblastoid cell lines generated fromschizophrenicor non-schizophrenicindividuals. We further found that miR-382 directly regulates the expression of two genes, FGFR1 andSPRY4, which are downregulated in both the cultured olfactory cells and LCM-OE derived fromschizophreniapatients. These genes are involved in the fibroblast growth factor (FGF) signaling pathway, while impairment of this pathway may underlie abnormal brain development and function associated withschizophrenia. Our data suggest that miR-382 elevation detected in patients' OE-derived samples might serve to strengthen current biomarker studies inschizophrenia. This study also illustrates the potential utility of OE-derived tissues and cells as surrogate samples for the brain. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Neurobiol. Dis. 2013 Jul 55: 1-10 |
| PMID | 23542694 |
| Title | MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients. |
| Abstract | schizophreniais a common neuropsychiatric disorder that has a strong genetic component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and psychiatric disorders includingschizophrenia, as indicated by their dysregulation in post-mortem brain tissues and in peripheral blood ofschizophreniapatients. The olfactory epithelium (OE) is one of the few accessible neural tissues that contain neurons and their stem cells. Previous studies showed that OE-derived tissues and cells can be safely and easily collected from live human subjects and may provide a "window" into neuronal processes involved in disorders such asschizophrenia, while avoiding the limitations of using postmortem brain samples or non-neuronal tissues. In this study, we found that the brain-enriched miR-382 (miR-382-5p) expression was elevated in in vitro cultured olfactory cells, in a cohort of sevenschizophreniapatients compared with seven non-schizophreniccontrols. MiR-382 elevation was further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE), enriched for mature olfactory neurons, in a cohort of 18schizophreniapatients and 18 non-schizophreniccontrols. In sharp contrast, miR-382 expression could not be detected in lymphoblastoid cell lines generated fromschizophrenicor non-schizophrenicindividuals. We further found that miR-382 directly regulates the expression of two genes, FGFR1 andSPRY4, which are downregulated in both the cultured olfactory cells and LCM-OE derived fromschizophreniapatients. These genes are involved in the fibroblast growth factor (FGF) signaling pathway, while impairment of this pathway may underlie abnormal brain development and function associated withschizophrenia. Our data suggest that miR-382 elevation detected in patients' OE-derived samples might serve to strengthen current biomarker studies inschizophrenia. This study also illustrates the potential utility of OE-derived tissues and cells as surrogate samples for the brain. |
| SCZ Keywords | schizophrenia, schizophrenic |